Blood Dendritic Cell Antigen 2 (BDCA-2) is a single-pass transmembrane type of membrane protein. BDCA-2 is known to be expressed restrictively in human plasmacytoid dendritic cells (pDCs). BDCA-2 plays a role in controlling functions of pDCs by transmitting signal into pDCs (Int. Immunol., Vol. 25, p. 271-277, 2013).
BDCA-2 is known to function with respect to activated immune responses in an inhibitory manner (Non-Patent Document 1). The details of this mechanism is still unclear in many parts, but as described later, it has been reported that pDCs in the activated state can be inhibited by crosslinking BDCA-2 molecules using an antibody against BDCA-2 (Patent Document 1, and Non-Patent Documents 1 to 4).
It is known that pDCs, which are the cells specifically expressing BDCA-2, are abnormally activated in peripheral blood or disorder sites and produce interferon (IFN) α in a large amount, in autoimmune diseases such as systemic lupus erythematosus, scleroderma, polymyositis and dermatomyositis, psoriasis, Sjoegren's syndrome, rheumatoid arthritis, Grave's disease, and Hashimoto's disease. It has been found that pDCs are deeply involved in the pathology of autoimmune diseases (Arthritis Rheum., Vol. 65, p. 853-863, 2013).
It has been reported that in systemic lupus erythematosus, which is a type of autoimmune disease, there is a positive correlation to the severity and the concentration of IFN α in the blood of patients (Lupus, Vol. 9, p. 664-671, 2000). Further, when model mice with systemic lupus erythematosus pathology are subjected to genetic modification so as not to generate pDCs, the onset of systemic lupus erythematosus is inhibited. From this viewpoint, the involvement of pDCs in systemic lupus erythematosus pathology has been demonstrated directly (Proc. Natl. Acad. Sci. USA, Vol. 110, p. 2940-2945, 2013).
As an antibody against human BDCA-2, AC144 which is a mouse monoclonal antibody is known (Patent Document 1, and Non-Patent Documents 1 to 4), and it has been reported that AC144 can inhibit pDCs in the activated state by crosslinking the BDCA-2 molecules. Specifically, it has been reported that production of IFNα or the like induced from pDCs stimulated by ligand to a Toll-like receptor (TLR) 9 can be inhibited by using AC144 (Non-Patent Documents 1 to 4). It has also been reported that use of the serum from systemic lupus erythematosus patients in a stimulant induces IFNα production from pDCs, and this IFNα production can also be similarly inhibited by using AC144 (Non-Patent Document 4).